A New Domino Process Initiated by Acetylide Addition onto trans-1,2-­Dibenzoyl-3,5-cyclohexadienes: Observation of Sequential C-C, C-O Bond Formation/Cleavage Reactions

Abstract

Domino acetylide addition/rearrangement reactions on trans-1,2-dibenzoyl-3,5-cyclohexadienes with lithium acetylides furnish stereodefined 3-ylidene-2,3-dihydrofurans and polysubstituted benzophenones; the overall domino process entails three bond formations (two C-C and one C-O) and two bond cleavages (one C-C and one C-O) in a single operation.

domino reaction - zirconacycle - acetylide addition - 3-ylidene-2,3-dihydrofurans - benzophenones

References and Notes

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6a

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7

CCDC 294449 contains the crystallographic data for 3d. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

8

CCDC 294450 contains the crystallographic data for 4f. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

9

Typical Procedure for the Cycloaddition Reaction of Zirconacyclopentadienes with trans -1,4-Diphenylbut-2-ene-1,4-dione.
To a solution of Cp₂ZrCl₂ (0.32 g, 1.1 mmol) in THF (5 mL) was added n-BuLi (1.6 M THF solution, 2.2 mmol) at
-78 °C. After stirring for 1 h at the same temperature, 3-hexyne (0.16 g, 2 mmol) was added and the reaction mixture was warmed up to r.t. and stirred for 1 h. Then, BiCl₃ (0.38 g, 1.2 mmol), which was dried using a heat gun at ca. 500 °C for 30 min under vacuum, and 1,4-diphenyl-but-2-ene-1,4-dione (0.47 g, 2.0 mmol) were added and the mixture was stirred at 50 °C for 12 h. The reaction mixture was quenched with 3 N HCl and extracted with EtOAc. The extract was washed with H₂O, brine and dried over MgSO₄. The solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel (PE-EtOAc, 20:1). A light-yellow solid of 3a (265 mg, 66%) was obtained.
trans-(6-Benzoyl-2,3,4,5-tetraethylcyclohexa-2,4-dienyl)phenylmethanone(3a): ¹H NMR (Me₄Si, CDCl₃): δ = 0.77 (t, J = 7.5 Hz, 6 H), 0.98 (t, J = 7.5 Hz, 6 H), 1.66-1.78 (m, 2 H), 2.10-2.46 (m, 6 H), 4.08 (s, 2 H), 7.41-7.52 (m, 4 H), 7.52-7.57 (m, 2 H), 7.77-7.81 (m, 4 H). ¹³C NMR (Me₄Si, CDCl₃): δ = 13.0, 14.7, 20.7, 25.8, 49.2, 127.5, 128.0, 128.4, 132.2, 137.2, 137.7, 199.7. HRMS (MALDI/DHB): m/z calcd for C₂₈H₃₃O₂ [M + H]⁺: 401.2481; found: 401.2475.
Typical Procedure for the Domino Reactions of trans -1,2-Dibenzoyl-3,5-cyclohexadiene Products 3 with Lithium Acetylides.
To a solution of 1-hexyne (0.12 mL, 1.0 mmol) in THF (5 mL) was added n-BuLi (0.63 mL, 1.6 M in hexane) at
-78 °C. After the mixture was stirred at the same temperature for 1 h, the mixture was warmed up to 0 °C and stirred for 30 min. Then, (6-benzoyl-2,3,4,5-tetraethyl-cyclohexa-2,4-dienyl) phenylmethanone 3a (0.20 g, 0.5 mmol) was added; the resulting reaction mixture was warmed up to r.t. and stirred for 24 h. The mixture was quenched with an aq solution of NH₄Cl and extracted with EtOAc. The extract was washed with H₂O, brine and dried over MgSO₄. The solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel by first using a mixed solvent of PE-CH₂Cl₂ (25:1) as an eluent to give 4a (120 mg, 52%) as a white solid. Compound 5a (60 mg, 41%) was obtained as a yellow liquid by using a second eluent (PE-CH₂Cl₂, 1:1).
(E)-3-Butylidene-2,5-diphenyl-2-(2,3,4,5-tetraethyl-phenyl)-2,3-dihydrofuran (4a): column chromatography on silica gel (PE-CH₂Cl₂, 25:1) afforded 120 mg (52%) product as a white solid. ¹H NMR (Me₄Si, CDCl₃): δ = 0.92 (t, J = 7.4 Hz, 3 H), 1.03 (t, J = 7.1 Hz, 3 H), 1.09-1.26 (m, 9 H), 1.47 (q, J = 7.5 Hz, 2 H), 2.12-2.28 (m, 2 H), 2.54-2.73 (m, 8 H), 4.74 (t, J = 7.8 Hz, 1 H), 6.24 (s, 1 H), 7.18-7.36 (m, 9 H), 7.74 (d, J = 7.5Hz, 2 H). ¹³C NMR (Me₄Si, CDCl₃): δ = 13.9, 15.3, 15.4, 16.0, 16.1, 21.5, 21.8, 23.3, 23.6, 25.7, 32.0, 95.7, 98.2, 120.7, 125.4, 125.5, 126.6, 127.3, 127.8, 128.3, 128.7, 130.9, 136.9, 137.8, 140.1, 140.5, 142.2, 146.9, 146.9, 158.7. HRMS (MALDI/DHB): m/z calcd for C₃₄H₄₁O [M + H]⁺: 465.3157; found: 465.3152.
Phenyl(2,3,4,5-tetraethylphenyl)methanone (5a): column chromatography on silica gel (PE-CH₂Cl₂, 1: 1), product as a yellow liquid. ¹H NMR (Me₄Si, CDCl₃): δ = 1.10 (t, J = 7.5 Hz, 3 H), 1.18 (t, J = 7.5 Hz, 3 H), 1.20 (t, J = 7.5 Hz, 3 H), 1.21 (t, J = 7.5 Hz, 3 H), 2.59-2.78 (m, 8 H), 6.91 (s, 1 H), 7.41-7.46 (m, 2 H), 7.53-7.58 (m, 1 H), 7.82-7.85 (m, 2 H). ¹³C NMR (Me₄Si, CDCl₃): δ = 15.3, 15.4, 15.9, 16.5, 21.6, 22.0, 22.8, 25.5, 126.1, 128.2, 130.2, 130.3, 132.9, 137.1, 138.1, 138.1, 138.9, 140.8, 142.1, 199.8. HRMS (MALDI/DHB): m/z calcd for C₂₁H₂₇O [M + H]⁺: 295.2062; found: 295.2056.